Bacillus Calmette-Guérin vaccine for prevention of COVID-19 and other respiratory tract infections in older adults with comorbidities: a randomized controlled trial
Authors: Eva L. Koekenbier, Konstantin Fohse, Josephine S. van de Maat, Jan Jelrik Oosterheert, Cees van Nieuwkoop, Jacobien J. Hoogerwerf, Martin P. Grobusch, Maurice A.A.J. van den Bosch, Janneke H.H. van de Wijgert, Mihai G. Netea, Frits R. Rosendaal, Marc J.M. Bonten, C.H. (Henri) van Werkhoven, Astrid Aardenburg-van Huisstede, Heidi S.M. Ammerlaan, Willem G. Boersma, Marc J.M. Bonten, Maurice A.A.J. van den Bosch, Kees Brinkman, Patricia C.J. Bruijning-Verhagen, Reinout van Crevel, Corine Delsing, Thijs ten Doesschaten, Anton S.M. Dofferhoff, Ruud Duijkers, Konstantin Fohse, Martin P. Grobusch, Rolf H.H. Groenwold, Corine de Haas, Robert-Jan Hassing, Marieke L.A. de Hoog, Jacobien J. Hoogerwerf, Susanne M. Huijts, Astrid van Hylckama-Vlieg, Eefje Jong, Hanna K. de Jong, Martijn Knap, Eva L. Koekenbier, Michael Koenders, Ilse J.E. Kouijzer, Henk Kramer, Roel van de Laar, Arief Lalmohamed, Karel-Jan D.F. Lensen, Willem M. Lijfering, Josephine S. van de Maat, Fabienne Magdelijns, Bob Meek, Rutger A. Middelburg, Hazra S. Moeniralam, Simon P. Mooijaart, Barbara C. van Munster, Mihai G. Netea, Cees van Nieuwkoop, Jaap ten Oever, Jan Jelrik Oosterheert, Marc Padros Goossens, Vincent Peters, Douwe F. Postma, Niels Pouw, Herre J. Reesink, Marieke J.A. de Regt, Anneli C.J. van der Reijden, Frits R. Rosendaal, R. Schaakxs, Kitty Slieker, Robbert J. Slingerland, Nicolette L.J. van Sluis, Coen D.A. Stehouwer, Frank van de Veerdonk, Annelies Verbon, C.H. (Henri) van Werkhoven, Janneke H.H. van de Wijgert
Journal: Clinical Microbiology and Infection (2023)

ObjectivesTo test whether Bacillus Calmette-Guérin (BCG) vaccination would reduce the incidence of COVID-19 and other respiratory tract infections (RTIs) in older adults with one or more comorbidities.MethodsCommunity-dwelling adults aged 60 years or older with one or more underlying comorbidities and no contraindications to BCG vaccination were randomized 1:1 to BCG or placebo vaccination and followed for 6 months. The primary endpoint was a self-reported, test-confirmed COVID-19 incidence. Secondary endpoints included COVID-19 hospital admissions and clinically relevant RTIs (i.e. RTIs including but not limited to COVID-19 requiring medical intervention). COVID-19 and clinically relevant RTI episodes were adjudicated. Incidences were compared using Fine-Gray regression, accounting for competing events.ResultsA total of 6112 participants with a median age of 69 years (interquartile range, 65–74) and median of 2 (interquartile range, 1–3) comorbidities were randomized to BCG (n = 3058) or placebo (n = 3054) vaccination. COVID-19 infections were reported by 129 BCG recipients compared to 115 placebo recipients [hazard ratio (HR), 1.12; 95% CI, 0.87–1.44]. COVID-19-related hospitalization occurred in 18 BCG and 21 placebo recipients (HR, 0.86; 95% CI, 0.46–1.61). During the study period, 13 BCG recipients died compared with 18 placebo recipients (HR, 0.71; 95% CI, 0.35–1.43), of which 11 deaths (35%) were COVID-19-related: six in the placebo group and five in the BCG group.Clinically relevant RTI was reported by 66 BCG and 72 placebo recipients (HR, 0.92; 95% CI, 0.66–1.28).DiscussionBCG vaccination does not protect older adults with comorbidities against COVID-19, COVID-19 hospitalization, or clinically relevant RTIs.